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International audience; Background/objectives: While excessive food consumption represents a key factor in the development of obesity, the underlying mechanisms are still unclear. Ghrelin, a gut-brain hormone involved in the regulation of appetite, is impaired in obesity. In addition to its role in eating behavior, this hormone was shown to affect brain regions controlling reward, including the striatum and prefrontal cortex, and there is strong evidence of impaired reward processing in obesity. The present study investigated the possibility that disrupted reward-related brain activity in obesity relates to ghrelin deficiency.Subjects/methods: Fifteen severely obese subjects (BMI > 35 kg/m(2)) and fifteen healthy non-obese control subjects (BMI < 30 kg/m(2)) were recruited. A guessing-task paradigm, previously shown to activate the ventral striatum, was used to assess reward-related brain neural activity by functional magnetic resonance imaging (fMRI). Fasting blood samples were collected for the measurement of circulating ghrelin.Results: Significant activations in the ventral striatum, ventromedial prefrontal cortex and extrastriate visual cortex were elicited by the fMRI task in both obese and control subjects. In addition, greater reward-related activations were present in the dorsolateral prefrontal cortex, and precuneus/posterior cingulate of obese subjects compared to controls. Obese subjects exhibited longer choice times after repeated reward and lower circulating ghrelin levels than lean controls. Reduced ghrelin levels significantly predicted slower post-reward choices and reward-related hyperactivity in dorsolateral prefrontal cortices in obese subjects.Conclusion: This study provides evidence of association between circulating ghrelin and reward-related brain activity in obesity and encourages further exploration of the role of ghrelin system in altered eating behavior in obesity.

The objects located straight-ahead of the body are preferentially processed by the visual system. They are more rapidly detected and evoke stronger BOLD responses in early visual areas than elements that are retinotopically identical but located at eccentric spatial positions. To characterize the dynamics of the underlying neural mechanisms, we recorded in 29 subjects the EEG responses to peripheral targets differing solely by their locations with respect to the body. Straight-ahead stimuli led to stronger responses than eccentric stimuli for several components whose latencies ranged between 70 and 350 ms after stimulus onset. The earliest effects were found at 70 ms for a component that originates from occipital areas, the contralateral P1. To determine whether the straight-ahead direction affects primary visual cortex responses, we performed an additional experiment (n = 29) specifically designed to generate two robust components, the C1 and C2, whose cortical origins are constrained within areas V1, V2 and V3. Our analyses confirmed all the results of the first experiment and also revealed that the C2 amplitude between 130 and 160 ms after stimulus onset was significantly stronger for straight-ahead stimuli. A frequency analysis of the pre-stimulus baseline revealed that gaze-driven alterations in the visual hemi-field containing the straight-ahead direction were associated with a decrease in alpha power in the contralateral hemisphere, suggesting the implication of specific neural modulations before stimulus onset. Altogether, our EEG data demonstrate that preferential responses to the straight-ahead direction can be detected in the visual cortex as early as about 70 ms after stimulus onset. Electronic supplementary material The online version of this article (10.1007/s00429-019-01988-5) contains supplementary material, which is available to authorized users.

International audience; Residing at high altitude may lead to reduced blood oxygen saturation in the brain and altered metabolism in frontal cortical brain areas, probably due to chronic hypobaric hypoxia. These changes may underlie the increased rates of depression and suicidal behavior that have been associated with life at higher altitudes. To test the hypothesis that hypobaric hypoxia is responsible for development of mood disorders due to alterations in neurochemistry, we assessed depression-like behavior in parallel to levels of brain metabolites in rats housed at simulated altitude. 32 female Sprague Dawley rats were housed either in a hypobaric hypoxia chamber at 10,000 ft of simulated altitude for 1 week or at local conditions (4500 ft of elevation in Salt Lake City, Utah). Depression-like behavior was assessed using the forced swim test (FST) and levels of neurometabolites were estimated by in vivo proton magnetic resonance spectroscopy in the frontal cortex, the striatum and the hippocampus at baseline and after a week of exposure to hypobaric hypoxia. After hypoxia exposure the animals demonstrated increased immobility behavior and shortened latency to immobility in the FST. Elevated ratios of myo-inositol, glutamate, and the sum of myo-inositol and glycine to total creatine were observed in the frontal cortex of hypoxia treated rats. A decrease in the ratio of alanine to total creatine was also noted. This study shows that hypoxia induced alterations in frontal lobe brain metabolites, aggravated depression-like behavior and might be a factor in increased rates of psychiatric disorders observed in populations living at high altitudes.

Atmospheric pressure fluctuations (APF) might induce mechanical effects in the pars flaccida (PF) of the eardrum. To clarify these effects, different kinds of pressure oscillations (PO), chosen within the range of naturally occurring APF, were applied to the middle ears (ME) of gerbils. The linear displacement of the PF during a PO in the ME was measured by laser interferometry. The compliance of the PF to PO was calculated as the ratio of the amplitude of a PF oscillation to the amplitude of a PO. The displacement of the PF traced the PO in the entire range of frequencies (from 10 mHz to 200 mHz) and amplitudes (from 10 Pa to 110 Pa) applied to the ME. Moreover, the PF is found to be displaced by pressure pulses of a few pascals only using a PO with a complex shape. The differences found in the compliance of the PF due to PO with low (less than 20 Pa) and high (more than 90 Pa) amplitude point out that the mechanism of pressure regulation in the ME through the mechanical reaction of the PF in gerbil ears is better adapted to ordinary levels of natural APF than to extraordinary levels. The implications of these findings for the physiology of the human ME with respect to adaptation to natural APF are discussed.

International audience; The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n=7), increased (n=10) or stayed unchanged (n=7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety.

International audience; Background: Alexithymia, the inability to describe one's own emotions, is linked to deficits in empathy, manifesting as a diminished capacity to recognize or understand the emotions and mental states of others. Several brain centers of autonomic control and interoception that are activated in empathy are thought to misfunction in alexithymia. We hypothesized that individual differences in autonomic changes under affective stimulation might be associated with differences in alexithymia and empathy. Methods: We studied 21 healthy volunteers, comparing their alexithymia and empathy scores with changes in their sympathetic autonomic arousal, indexed by the palmar skin potential level, during 3 tasks: playing a computer game, performing mental arithmetic, and watching a negative emotional valence video. Results: Both autonomic and subjective sense of arousal increased at the beginning of each task and then gradually subsided over the course of the task. Higher autonomic arousal at the onset of the computer game was associated with higher empathy scores, and at the onset of the negative video with higher scores for both empathy and alexithymia. Alexithymia delayed the habituation of autonomic arousal during the computer game, while the empathy score was related to a faster decline in arousal during the negative video task. Conclusions: High alexithymia and high empathy scores were linked to increased autonomic arousal at the onset of emotional stimulation, but were distinguishable in the rates of habituation of the evoked arousal. Our data provide insight into the relationships among interacting psychological traits, physiologic regulation, and the arousal dimension of emotional experience.

This study was designed to clarify whether the pars flaccida (PF) as a flexible part of the tympanic membrane is capable of reacting to pressure oscillations (PO) with amplitudes and frequencies typical for natural atmospheric pressure fluctuations in the far infrasound frequency range (APF). If so, the PF mechanical reactions to APF might be involved in the overall physiologic regulation processes, which make organisms susceptible to APF. The displacements of the PF in response to PO were measured in vitro in ears of gerbils and rabbits by means of laser Doppler vibrometry. The index of the PF reactivity (R(a)) was determined as the ratio of the amplitude of the PF oscillations (PFO) to the amplitude of the PO. All kinds of PO applied caused PFO. The amplitude of the PFO increased when the amplitude of the PO was increased. In gerbils, a decrease in R(a) with the increase in amplitude of the PO was observed. In the range of PO lowest amplitudes (4-20 Pa) R(a) proved to be 1.4 times higher than in the range of highest amplitudes (90-105 Pa). Considering that the natural APF are usually within the range of +/-20 Pa, this fact points to an important contribution of the PF to the pressure dynamics in the middle ear (ME) of gerbils. In rabbit ears, R(a) was lower and recovery from plastic deformation was slower than in gerbils. Our findings are in line with the suggestion that the PF might play an important role in respect of adaptation to natural APF.

Background Migraine is characterized pathophysiologically by an interictal habituation deficit of information processing, responsible for cortical hyperresponsiveness, which normalizes during attacks [1]. Furthermore, descending pain control systems (DPCSs) can be impaired in episodic and chronic migraine [3,4]. Noninvasive neuromodulation of the cerebral cortex may be effective in migraine prophylaxis [2] including, in chronic migraine, modulation of the dorsolateral prefrontal cortex (DLPFC) that is part of the DPCSs [5].

To investigate the role of protein tyrosine phosphorylation in gastric wound formation and repair following ulceration.Gastric lesions were induced in rats using restraint cold stress. To investigate the effect of oxidative and nitrosative cell stress on tyrosine phosphorylation during wound repair, total activity of protein tyrosine kinase (PTK), protein tyrosine phosphatase (PTP), antioxidant enzymes, nitric oxide synthase (NOS), 2',5'-oligoadenylate synthetase, hydroxyl radical and zinc levels were assayed in parallel.Ulcer provocation induced an immediate decrease in tyrosine kinase (40% in plasma membranes and 56% in cytosol, P0.05) and phosphatase activity (threefold in plasma membranes and 3.3-fold in cytosol), followed by 2.3-2.4-fold decrease (P0.05) in protein phosphotyrosine content in the gastric mucosa. Ulceration induced no immediate change in superoxide dismutase (SOD) activity, 30% increase (P0.05) in catalase activity, 2.3-fold inhibition (P0.05) of glutathione peroxidase, 3.3-fold increase (P0.05) in hydroxyl radical content, and 2.3-fold decrease (P0.05) in zinc level in gastric mucosa. NOS activity was three times higher in gastric mucosa cells after cold stress. Following ulceration, PTK activity increased in plasma membranes and reached a maximum on day 4 after stress (twofold increase, P0.05), but remained inhibited (1.6-3-fold decrease on days 3, 4 and 5, P0.05) in the cytosol. Tyrosine phosphatases remained inhibited both in membranes and cytosol (1.5-2.4-fold, P0.05). NOS activity remained increased on days 1, 2 and 3 (3.8-, 2.6-, 2.2-fold, respectively, P0.05). Activity of SOD increased 1.6 times (P0.05) days 4 and 5 after stress. Catalase activity normalized after day 2. Glutathione peroxidase activity and zinc level decreased (3.3- and 2-fold, respectively, P0.05) on the last day. Activity of 2',5'-oligoadenylate synthethase increased 2.8-fold (P0.05) at the beginning, and 1.6-2.3-fold (P0.05) during ulcer recuperation, and normalized on day 5, consistent with slowing of inflammation processes.These studies show diverse changes in total tyrosine kinase activity in gastric mucosa during the recovery process. Oxidative and nitrosative stress during lesion formation might lead to the observed reduction in tyrosine phosphorylation during ulceration.